1. Field of the Invention
The present invention relates to alkaloid aminoester derivatives, which act as muscarinic receptor antagonists. The present invention also relates to processes for preparing such a compound and compositions which contain such a compound. The present invention further relates to methods of treating and/or preventing various conditions and/or diseases by administering such a compound.
2. Discussion of the Background
Quaternary ammonium salts, which act as muscarinic (M) receptor antagonist drugs, are currently used in therapy to induce bronchodilation for the treatment of respiratory diseases. Examples of well known M receptor antagonists are represented by ipratropium bromide and tiotropium bromide.
Several chemical classes acting as selective M3 receptor antagonist drugs have been developed for the treatment of inflammatory or obstructive airway diseases such as asthma and chronic obstructive pulmonary disease (COPD).
Quinuclidine carbamate derivatives and their use as M3 antagonists are disclosed in WO 02/051841, WO 03/053966 and WO 2008/012290.
Said M and M3 receptor antagonists are currently administered through inhalation in order to deliver the drug directly at the site of action and hence limiting the systemic exposure. However, even though the systemic exposure may be reduced through the inhalatory route, the compounds of the prior art may still exhibit undesired side effects due to systemic absorption. It is hence highly desirable to provide M3 receptor antagonists which are able to act locally, while having high potency and long duration of action. Said drugs, once adsorbed, are degraded to inactive compounds which are deprived of any systemic side effects typical of muscarinic antagonists.
U.S. Pat. No. 2,824,106 discloses quaternary alkyl derivatives of the tropeine series with increased spasmolytic activity and in particular N-phenyl amino acetyl derivatives.
J. Med. Chem., 1994, 37, 1712-1719 refers to presynaptic cholinergic modulators as potent cognition enhancers and analgesic drugs and in particular to N-phenyl amino acetyl derivatives.
U.S. Pat. No. 2,856,407 discloses aminoacid esters of hydroxypiperidines; among them are N-methyl-3-piperidyl-2′-N′-dimethylaminoacetate and N-methyl-4-piperidyl-2′-N′-dimethylaminoacetate.
WO 99/20612 describes compounds that inhibit the farnesylation of mutant ras gene products and in particular 4-(methylsulfanyl) butanoate derivatives.
WO 2008/053158 refers to inhibitors of p38 MAP kinase activity, useful in the treatment of inflammatory and autoimmune disease and in particular to methylpiperidin-4-yl L-leucinate derivatives.
Khimiko-Farmatsevticheskii Zhumal, (1977), 11(7), 30-5 refers to tropine ester of phenylglyoxylic acid and in particular to phenylalanine ester derivatives.
Chemical & Pharmaceutical Bulletin, (1971), 19(12), 2603-8 describes the one-step synthesis of atropine and other related alkaloids from dl-phenylalanine 3α-tropanyl ester and in particular to phenylalanine ester derivatives.
However, there remains a need for M3 receptor antagonists which are able to act locally, while having high potency and long duration of action.